title: Influence of selective fluorination on the biological activity and proteolytic stability of glucagon-like peptide-1.
abstract: The relative simplicity and high specificity of peptide therapeutics has fueled recent interest. However, peptide and protein drugs generally require injection and suffer from low metabolic stability. We report here the design, synthesis, and characterization of fluorinated analogues of the gut hormone peptide, GLP-1. Overall, fluorinated GLP-1 analogues displayed higher proteolytic stability with simultaneous retention of biological activity (efficacy). Fluorinated amino acids are useful for engineering peptide drug candidates and probing ligand-receptor interactions.
authors.affiliation: Department of Chemistry, Tufts University, Medford, Massachusetts 02155, USA.
authors.forename: He
authors.initials: H
authors.lastname: Meng
authors.forename: Subrahmanian Tarakkad
authors.initials: ST
authors.lastname: Krishnaji
authors.forename: Martin
authors.initials: M
authors.lastname: Beinborn
authors.forename: Krishna
authors.initials: K
authors.lastname: Kumar
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002522:Chlorocebus aethiops; D015195:Drug Design; D052216:Glucagon-Like Peptide 1 / Q000138:chemical synthesis / Q000737:chemistry*; D054879:Halogenation; D007930:Leucine / Q000031:analogs & derivatives* / Q000737:chemistry; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D055550:Protein Stability
chemical_list: C445784:hexafluoroleucine; D052216:Glucagon-Like Peptide 1; D007930:Leucine